Mammalian blood contains a wide variety of different types of cells, including red blood cells (erythrocytes), platelets, and white blood cells (leukocytes). White blood cells (leukocytes), in turn, include several different cell types, notably the lymphocytes, monocytes, and several types of granulocytes such as neutrophils, eosinophils, and basophils. These various types of cells comprise a major part of the complex and critical mammalian immune system. Most of them are short lived and must be replaced every few hours, days, weeks, or months, and all of them are formed by differentiation and proliferation of a single type of pluripotent stem cells which reside in the bone marrow.
The process by which a single kind of stem cell differentiates to form many different mature cells which cannot themselves proliferate is called hematopoiesis. It involves the formation of precursors for each of these different kinds of cells from a single kind of stem cell, which occurs in bone marrow, and proliferation and differentiation into the specialized cell types, which occurs principally in the bone marrow, spleen, thymus, and lymph nodes. The process is controlled by a complex system of signals that attempts to maintain an appropriate balance among all of these different types of cells so that the immune system operates effectively.
Some disease states and infections dramatically affect hematopoiesis, resulting in depletion of certain types of blood cells. For example, HIV infection often causes anemia (red blood cell deficiency), neutropenia (neutrophil deficiency), or thrombocytopenia (platelet deficiency), or various combinations of these states, including pancytopenia, which is a deficiency of all different types of blood cells. See N. K. Banda, et al., Depletion of CD34+CD4+ Cells in Bone Marrow from HIV-1 Infected Individuals, Biol. Blood and Marrow Transplantation, 5(3), 162–172 (1999). See also D. Fuchs, et al., AIDS, 5(2), 209–212 (1991)Similarly, various radiation and chemotherapy regimens may severely compromise the immune system by depleting one or more of these cell types. See C. L. Mackall, Stem Cells 18, 10–18 (2000). Radiation therapy, for example, can destroy most of the highly sensitive and surprisingly rare stem cells, resulting in an inability to rapidly regenerate cellular components of the blood.
Regardless of whether it is caused by an organic disorder, infection, or therapeutic treatment, severe deficiency of any of these cellular components of the blood and the immune system can result in direct physical symptoms (such as anemia where red blood cells are depleted, or bleeding disorders where platelets are depleted) or in greatly increased susceptibility to secondary infections. Thus methods for treating deficiencies of various types of blood cells are needed, as are methods for preventing such deficiencies that would otherwise result from treatment of other disorders such as cancers or viral infections. The present invention provides methods for increasing levels of various types of blood cells in a subject experiencing a deficiency in the level of one or more types of blood cells.